The nonessential amino acid serine is involved in many different biological reactions. It can be formed from, and reconverted to, glycolytic intermediates at the level of the phosphoglycerates. It is utilized in the formation of complex lipids, e.g. phosphatidyl serine and sphingolipids, and is an important source of one carbon compounds that are utilized in the de novo biosynthesis of the purine ring and of the methyl group of thymine. It is also a precursor of cysteine and glycine; with respect to the latter, neurochemical and neurophysiological evidence reported recently supports the role of glycine as an inhibitory neurotransmitter. In view of the diverse biological functions of serine, the overall objective of this project is to study the interrelationships and importance of the different pathways for the metabolism of serine, glycine and one carbon tetrahydrofolate derivatives in different mammalian systems as well as possible regulatory mechanisms involved. The effects of different hormones, e.g. insulin, glucagon, sex hormones, etc., and different dietary conditions on the levels of activity of enzymes of serine, glycine and one carbon compounds in different organs of fetal and adult animals will be continued. Enzymes under investigation include phosphoglycerate dehydrogenase, D- glycerate dehydrogenase, P-serine phosphatase, serine transhydroxymethylase, the glycine cleavage system and methylene- tetrahydrofolate dehydrogenase. In addition, studies on the distribution and subcellular localization of these and other enzymes in different areas of brain and spinal cord will be studied. Purification of certain enzymes is in progress not only to permit more definitive studies with respect to their regulatory properties but also to be used as antigens in projected immunological studies. Assay conditions and other methodology for studies of this type have been established in this laboratory.